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101.
Coral bleaching response index: a new tool to standardize and compare susceptibility to thermal bleaching 下载免费PDF全文
Timothy D. Swain Jesse B. Vega‐Perkins William K. Oestreich Conrad Triebold Emily DuBois Jillian Henss Andrew Baird Margaret Siple Vadim Backman Luisa Marcelino 《Global Change Biology》2016,22(7):2475-2488
As coral bleaching events become more frequent and intense, our ability to predict and mitigate future events depends upon our capacity to interpret patterns within previous episodes. Responses to thermal stress vary among coral species; however the diversity of coral assemblages, environmental conditions, assessment protocols, and severity criteria applied in the global effort to document bleaching patterns creates challenges for the development of a systemic metric of taxon‐specific response. Here, we describe and validate a novel framework to standardize bleaching response records and estimate their measurement uncertainties. Taxon‐specific bleaching and mortality records (2036) of 374 coral taxa (during 1982–2006) at 316 sites were standardized to average percent tissue area affected and a taxon‐specific bleaching response index (taxon‐BRI) was calculated by averaging taxon‐specific response over all sites where a taxon was present. Differential bleaching among corals was widely variable (mean taxon‐BRI = 25.06 ± 18.44%, ±SE). Coral response may differ because holobionts are biologically different (intrinsic factors), they were exposed to different environmental conditions (extrinsic factors), or inconsistencies in reporting (measurement uncertainty). We found that both extrinsic and intrinsic factors have comparable influence within a given site and event (60% and 40% of bleaching response variance of all records explained, respectively). However, when responses of individual taxa are averaged across sites to obtain taxon‐BRI, differential response was primarily driven by intrinsic differences among taxa (65% of taxon‐BRI variance explained), not conditions across sites (6% explained), nor measurement uncertainty (29% explained). Thus, taxon‐BRI is a robust metric of intrinsic susceptibility of coral taxa. Taxon‐BRI provides a broadly applicable framework for standardization and error estimation for disparate historical records and collection of novel data, allowing for unprecedented accuracy in parameterization of mechanistic and predictive models and conservation plans. 相似文献
102.
Karine Robitaille Jillian L. Rourke Joanne E. McBane Accalia Fu Stephen Baird Qiujiang Du Tatsuya Kin A. M. James Shapiro Robert A. Screaton 《The Journal of biological chemistry》2016,291(9):4614-4625
The expansion of cells for regenerative therapy will require the genetic dissection of complex regulatory mechanisms governing the proliferation of non-transformed human cells. Here, we report the development of a high-throughput RNAi screening strategy specifically for use in primary cells and demonstrate that silencing the cell cycle-dependent kinase inhibitors CDKN2C/p18 or CDKN1A/p21 facilitates cell cycle entry of quiescent adult human pancreatic beta cells. This work identifies p18 and p21 as novel targets for promoting proliferation of human beta cells and demonstrates the promise of functional genetic screens for dissecting therapeutically relevant state changes in primary human cells. 相似文献
103.
Judi Kidger Nicholas Turner William Hollingworth Rhiannon Evans Sarah Bell Rowan Brockman Lauren Copeland Harriet Fisher Sarah Harding Jillian Powell Ricardo Araya Rona Campbell Tamsin Ford David Gunnell Simon Murphy Richard Morris 《PLoS medicine》2021,18(11)
BackgroundTeachers are at heightened risk of poor mental health and well-being, which is likely to impact on the support they provide to students, and student outcomes. We conducted a cluster randomised controlled trial, to test whether an intervention to improve mental health support and training for high school teachers led to improved mental health and well-being for teachers and students, compared to usual practice. We also conducted a cost evaluation of the intervention.Methods and findingsThe intervention comprised (i) Mental Health First Aid training for teachers to support students; (ii) a mental health awareness session; and (iii) a confidential staff peer support service. In total 25 mainstream, non-fee-paying secondary schools stratified by geographical area and free school meal entitlement were randomly allocated to intervention (n = 12) or control group (n = 13) after collection of baseline measures. We analysed data using mixed-effects repeated measures models in the intention-to-treat population, adjusted for stratification variables, sex, and years of experience. The primary outcome was teacher well-being (Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were teacher depression, absence, and presenteeism, and student well-being, mental health difficulties, attendance, and attainment. Follow-up was at months 12 (T1) and 24 (T2). We collected process data to test the logic model underpinning the intervention, to aid interpretation of the findings. A total of 1,722 teachers were included in the primary analysis. Teacher well-being did not differ between groups at T2 (intervention mean well-being score 47.5, control group mean well-being score 48.4, adjusted mean difference −0.90, 95% CI –2.07 to 0.27, p = 0.130). The only effect on secondary outcomes was higher teacher-reported absence among the intervention group at T2 (intervention group median number of days absent 0, control group median number of days absent 0, ratio of geometric means 1.04, 95% CI 1.00 to 1.09, p = 0.042). Process measures indicated little change in perceived mental health support, quality of relationships, and work-related stress. The average cost of the intervention was £9,103 per school. The study’s main limitations were a lack of blinding of research participants and the self-report nature of the outcome measures.ConclusionsIn this study, we observed no improvements to teacher or student mental health following the intervention, possibly due to a lack of impact on key drivers of poor mental health within the school environment. Future research should focus on structural and cultural changes to the school environment, which may be more effective at improving teacher and student mental health and well-being.Trial registrationwww.isrctn.com ISRCTN95909211.Using a cluster randomized study, Judi Kidger and colleagues study an intervention to improve teacher wellbeing support and training to support students in UK high schools (the WISE study). 相似文献
104.
Direct Microbial Reduction and Subsequent Preservation of Uranium in Natural Near-Surface Sediment 总被引:4,自引:1,他引:3 下载免费PDF全文
Yohey Suzuki Shelly D. Kelly Kenneth M. Kemner Jillian F. Banfield 《Applied microbiology》2005,71(4):1790-1797
The fate of uranium in natural systems is of great environmental importance. X-ray absorption near-edge spectroscopy (XANES) revealed that U(VI) was reduced to U(IV) in shallow freshwater sediment at an open pit in an inactive uranium mine. Geochemical characterization of the sediment showed that nitrate, Fe(III), and sulfate had also been reduced in the sediment. Observations of the sediment particles and microbial cells by scanning and transmission electron microscopy, coupled with elemental analysis by energy dispersive spectroscopy, revealed that uranium was concentrated at microbial cell surfaces. U(IV) was not associated with framboidal pyrite or nanometer-scale iron sulfides, which are presumed to be of microbial origin. Uranium concentrations were not detected in association with algal cells. Phylogenetic analyses of microbial populations in the sediment by the use of 16S rRNA and dissimilatory sulfite reductase gene sequences detected organisms belonging to the families Geobacteraceae and Desulfovibrionaceae. Cultivated members of these lineages reduce U(VI) and precipitate iron sulfides. The association of uranium with cells, but not with sulfide surfaces, suggests that U(VI) is reduced by the enzymatic activities of microorganisms. Uranium was highly enriched (760 ppm) in a subsurface black layer in unsaturated sediment sampled from a pit which was exposed to seasonal fluctuations in the pond level. XANES analysis showed that the majority of uranium in this layer was U(IV), indicating that uranium is preserved in its reduced form after burial. 相似文献
105.
106.
Got milk? The secret life of laticifers 总被引:1,自引:0,他引:1
Laticifers are specialized cells that occur in over 20 plant families in several unrelated angiosperm orders. Although laticifers are likely to be of polyphyletic origin, their occurrence is considered a morphological indicator of relatedness among species. The classification of laticifers is based on developmental patterns and overall morphology. The cytoplasmic latex exuded in response to damage often includes specialized metabolites, such as cardenolides, alkaloids and natural rubber. Laticifers provide an effective location to store defense metabolites, although not all latex-bearing plants accumulate bioactive natural products. Ecophysiological studies have shown that latex and its associated metabolites are vital for the defense of plants against insects. The anatomy, development and physiology of laticifers are discussed with a focus on evolutionary and ecological perspectives. 相似文献
107.
108.
Jillian R. Brown Feng Yang Anjana Sinha Boopathy Ramakrishnan Yitzhak Tor Pradman K. Qasba Jeffrey D. Esko 《The Journal of biological chemistry》2009,284(8):4952-4959
The disaccharide peracetylated
GlcNAcβ1–3Galβ-O-naphthalenemethanol (disaccharide 1)
diminishes the formation of the glycan sialyl Lewis X
(Neu5Acα2–3Galβ1–4(Fucα1–3) GlcNAc;
sLeX) in tumor cells. Previous studies showed that the mechanism of
action of disaccharide 1 involves three steps: (i) deacetylation by
carboxyesterases, (ii) action as a biosynthetic intermediate for downstream
enzymes involved in sLeX assembly, and (iii) generation of several
glycans related to sLeX. In this report, we show that
GlcNAcβ1–3Galβ-O-naphthalenemethanol binds to the
acceptor site of human β1–4-galactosyltransferase much like the
acceptor trisaccharide, GlcNAcβ1–2Manβ1–6Man, which is
present on N-linked glycans. The 4′-deoxy analog, in which the
acceptor hydroxyl group was replaced by -H, did not act as a substrate but
instead acted as a competitive inhibitor of the enzyme. The acetylated form of
this compound inhibited sLeX formation in U937 monocytic leukemia
cells, suggesting that it had inhibitory activity in vivo as well. A
series of synthetic acetylated analogs of 1 containing -H, -F, -N3,
-NH2, or -OCH3 instead of the hydroxyl groups at
C-3′- and C-4′-positions of the terminal
N-acetylglucosamine residue also blocked sLeX formation in
cells. The reduction of sLeX by the 4′-deoxy analog also
diminished experimental tumor metastasis by Lewis lung carcinoma in
vivo. These data suggest that nonsubstrate disaccharides have therapeutic
potential through their ability to bind to glycosyltransferases in
vivo and to alter glycan-dependent pathologic processes.The sialylated, fucosylated tetrasaccharide,
sLeX,3 is a
common carbohydrate determinant present in many O-GalNAc-linked
mucins and N-linked glycans that act as selectin ligands (see Ref.
1 and references therein).
Expression of sLeX endows tumor cells with the capacity to bind to
platelets and endothelial cells in the vasculature via P- and E-selectins,
thus facilitating hematogenous metastasis possibly through protection against
innate immune cells and by adhesion to the blood vessel wall. Strategies for
blocking selectin-carbohydrate interactions include (i) competition by soluble
recombinant forms of selectins, glycoprotein ligands, and glycolipids, (ii)
peptides based on the primary sequence of the carbohydrate binding site, (iii)
anti-selectin antibodies, (iv) oligosaccharides related to LewisX,
(v) inositol polyanions and sulfated sugars, (vi) heparin, and (vii) molecular
mimics of sLeX, including oligonucleotides (reviewed in Refs.
2 and
3). Analogs of acceptor
substrates of the various glycosyltransferases involved in glycan biosynthesis
provide another class of potential inhibitors (reviewed in Refs.
4 and
5). Although many of these
analogs are effective in vitro, they generally do not exhibit
inhibitory activity in cells due to poor membrane permeability. The large
number of polar hydroxyl groups and the lack of membrane transporters for
oligosaccharides in most cells presumably prevent their uptake
(6).In contrast to many of the inhibitors described above, peracetylated
disaccharides (e.g. acetylated
Galβ1–4GlcNAcβ-O-naphthalenemethanol (NM), acetylated
Galβ1–3GalNAcα-O-NM, and acetylated
GlcNAcβ1–3Galβ-O-NM) inhibit sLeX biosynthesis in
cells
(6–9).
These compounds are taken up by cells by passive diffusion and acted on by
cytoplasmic or membrane-associated carboxyesterases, which remove the acetyl
groups. The compounds gain access to the biosynthetic enzymes located in the
Golgi complex, where they serve as substrates, priming oligosaccharide
synthesis and generating products related to O-GalNAc-linked mucin
oligosaccharides. Priming in this manner diverts the assembly of the
O-linked chains from endogenous glycoproteins, resulting in
inhibition of expression of terminal Lewis antigens that are recognized by
selectins. Inhibition occurs at a much lower dose than for
monosaccharide-based agents, such as GalNAcβ-O-benzyl (∼25
μm versus 1–2 mm, respectively)
(10,
11). Furthermore, the
disaccharides appear to selectively affect sLeX formation, since
sLea expression was unaffected
(12). By blocking selectin
ligand expression, these compounds block both experimental and spontaneous
metastasis (12,
13).In this study, we have examined acetylated disaccharide analogs that have
been modified so that after deacetylation their activity as substrates would
be altered. Characterization of the 4′-deoxy derivative using
β1–4-galactosyltransferase 1 as a model showed that it acts by
competitively inhibiting the enzyme. Interestingly, the peracetylated form of
this analog maintains the capacity to inhibit sLeX expression in
U937 lymphoma cells and Lewis lung carcinoma (LLC) cells and block tumor
formation in vivo. Thus, the deoxy analog presumably inhibits one or
more galactosyltransferases in vivo, thereby blocking sLeX
formation and experimental tumor cell metastasis without generation of
oligosaccharide products. 相似文献
109.
Kenneth R. Meehan Laleh Talebian Jillian Wu John M. Hill Zbigniew M. Szczepiorkowski Charles L. Sentman Marc S. Ernstoff 《Cytotherapy》2010,12(8):1013-1021
Background aimsA phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.MethodsInterleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte–macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2).ResultsToxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1–3) to collect 3.2 × 106 CD34+ cells/kg (median; range 1.9–6.6 × 106/kg). Immune mobilization increased the number of CD3+ CD8+ T cells (P = 0.002), CD56+ natural killer (NK) cells (P = 0.0001), CD8+ CD56+ T cells (P = 0.002) and CD4+ CD25+ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 × 106 IU/m2/day.ConclusionsImmune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution. 相似文献
110.